ABSTRACT
Objective: To determine the incidence of hypertension among children during the inductionand re-induction phases of acute lymphoblastic leukemia (ALL) therapy and association withpossible risk factors. Methods: A retrospective analysis of 208 consecutive pediatric (age<18 y) ALL patients, treated per BFM-95 protocol between January 2009 and December2013. Data were analyzed to determine the incidence of hypertension and risk factors for itsdevelopment. Results: Incidence of hypertension requiring antihypertensive medication,was 29% (61/208) during induction and 17% (33/198) during re-induction (P=0.003). Median(range) age of patients developing hypertension was 4 y (4 mo to 8 y). Age <10 y andpresence of constipation were independently predictive of hypertension by multivariateanalysis. Conclusion: The present study reports a high incidence of hypertension amongchildren undergoing ALL induction therapy.
ABSTRACT
Background & objectives: Mercaptopurine, azathioprine, and thioguanine, used as antineoplastic agents and immunosuppressants are catabolized by thiopurine methyltransferase (TPMT) enzyme, which exhibits genetic polymorphism. Genotyping patients and the population to which the patients belong, is important for effective treatment and reducing toxicity. There is a need for faster methods for genotyping. Hence the present study was planned to test the application of SNaPshot technique for analysis of the three common TPMT alleles: TPMT*2, TPMT*3A, and TPMT*3C in DNA from healthy Indian volunteers as well as to apply the method on cDNA samples obtained from children with acute lymphoblastic leukaemia (ALL). Method: A total of 120 healthy volunteers and 25 patients were analysed by multiplexed SNaPshot reaction. Genomic DNA was the template for most of the analyses, but additionally the cDNA synthesized for translocation detection was used as the template in case of patients with ALL. The results of SNaPshot reaction were confi rmed by direct sequencing. Results: The TPMT genotype could be reliably identifi ed by SNaPshot analysis in multiplex reactions both in genomic DNA samples and cDNA. The overall frequency of the three common polymorphisms was observed to be 4.9 per cent, arising from heterozygosity for TPMT*3C (4.1%) and TPMT*3A (0.8%). Interpretation & conclusion: SNaPshot method for TPMT polymorphism analysis works faster with the potential for high throughput. By simultaneously interrogating the genotype at multiple sites, the method can provide future opportunity to multiplex, though multiplexing has not been done in the present analysis. Heterozygosity for TPMT*3C (719 A>G) was detected in 4.1 per cent of the study population and no homozygosity was observed. Our results indicated that TPMT*3C was the most common polymorphism in Indian population, while TPMT3*A, associated with the absence of catalytic activity of TPMT, was very rare.